The impact of SF3B1 mutations in CLL on the DNA-damage response

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14740%2F15%3A00082250" target="_blank" >RIV/00216224:14740/15:00082250 - isvavai.cz</a>
Result on the web
<a href="http://www.nature.com/leu/journal/vaop/ncurrent/full/leu2014318a.html" target="_blank" >http://www.nature.com/leu/journal/vaop/ncurrent/full/leu2014318a.html</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1038/leu.2014.318" target="_blank" >10.1038/leu.2014.318</a>

Result language
angličtina
Original language name
The impact of SF3B1 mutations in CLL on the DNA-damage response
Original language description
Mutations or deletions in TP53 or ATM are well-known determinants of poor prognosis in chronic lymphocytic leukemia (CLL), but only account for approximately 40% of chemo-resistant patients. Genome-wide sequencing has uncovered novel mutations in the splicing factor sf3b1, that were in part associated with ATM aberrations, suggesting functional synergy. We first performed detailed genetic analyses in a CLL cohort (n=110) containing ATM, SF3B1 and TP53 gene defects. Next, we applied a newly developed multiplex assay for p53/ATM target gene induction and measured apoptotic responses to DNA damage. Interestingly, SF3B1 mutated samples without concurrent ATM and TP53 aberrations (sole SF3B1) displayed partially defective ATM/p53 transcriptional and apoptotic responses to various DNA-damaging regimens. In contrast, NOTCH1 or K/N-RAS mutated CLL displayed normal responses in p53/ATM target gene induction and apoptosis.
Czech name
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Czech description
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Type
J<sub>x</sub> - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)
CEP classification
FD - Oncology and haematology
OECD FORD branch
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Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year
2015
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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